Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data. The incidence of confirmed reinfection was 28.8 per 100 person-years PY, 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY 95%CI: 16.8-36.1. The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone hazard ratio HR: 2.45, 95%CI: 0.87-6.86, p=0.089, but did in confirmed and possible hepatitis C reinfections combined HR: 1.93, 95%CI: 1.01-3.69, p=0.047 and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection HR: 0.91; 95%CI: 0.83-0.98; p=0.019 and multiple recent injecting partners HR: 3.12; 95%CI: 1.08-9.00, p=0.035 were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection HR: 5.34, 95%CI: 1.67-17.03, p=0.005 and confirmed and possible reinfection HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033 than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear.Conclusions: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.